The skin is a vital organ composed of several layers (dermis, proliferative layers and stratum corneum), which covers the entire surface of the body and essentially serves as a barrier to the external environment. The quality and high functionality of the skin are directly linked to the water content of the different layers of the epidermis and the dermis. Thus, in a normal epidermis, the proliferative layers contain approximately 70% water, whereas the stratum corneum only contains 10 to 15% water.
Moisturization of the skin depends on three factors: the water supply provided by the circulation of physiological fluids, the loss of water to the external environment and finally the capacity of the various parts of the skin for containing water molecules.
The water supply is regulated by hormones (aldosterone, sexual hormones), pH or osmotic variations. Cellular membranes are inherently hydrophobic and therefore have low water-permeability, but there are water channels, namely pores which facilitate the flow of water and certain solutes.
Aquaporins are a type of transmembrane protein for transporting water and small molecules in solution. Type-3 aquaporins, or AQP3s, are present in the human epidermis, and more specifically in the keratinocytes of the proliferative layers of the epidermis (R. Sougrat et al., J. Invest. Dermatol., 2002). They are capable of transporting water and glycerol, the latter playing an important role in the constitution of the hydrolipidic film on the surface as well as maintaining the suppleness and sensory qualities of the stratum corneum. The moisturization and AQP3 content of the keratinocytes are directly linked. Thus, increasing AQP3s in the skin enables better moisturization of the epidermis (M. Dumas, J. Drugs Dermatol., 6 Jun. 2007). On the other hand, aquaporins play a role in the barrier function by positively regulating the establishment of links and tight-junction cellular communication (J. Kawedia et al., PNAS 104(9), 2007).
The corneal layers (strata cornea) form a barrier which is essential for limiting water loss. In the deepest layers of the stratum corneum, during the formation of corneocytes, insoluble profilaggrin present in granular keratinocytes turns into filaggrin and thus becomes capable of connecting to keratin fibers to form microfibrils. Filaggrin is also involved in maintaining the water content of the corneal layers. What will happen to it during corneocyte maturity depends on the water gradient in the stratum corneum. In normal skin, when there is low ambient humidity, filaggrin is hydrolyzed and releases hygroscopic and soluble substances composed of amino acids and amino acid derivatives which are part of the “Natural Moisturizing Factor”, or NMF. The NMF is able to collect water from the atmosphere and retain the water in the stratum corneum so as to maintain supple and flexible skin, and to allow the enzymatic reactions which are necessary for the corneocytes to evolve towards the final stage of desquamation. However, in certain conditions (e.g. xerosis, atopy), or even when the skin is aged, the NFM is of an insufficient quantity to ensure moisturizing functions or it can undergo degradation or cross over the cellular membrane, allowing the water to escape gradually, which evaporates in the external environment.
However, the main water reserves can be found in the dermis, which contains up to 80% water when the skin is young (this proportion is reduced with age). Dermal water derives from plasma and is directly linked to glycosaminoglycans (GAGs) and structural glycoproteins. The main function of the glycosaminoglycans is to ensure the structuring of collagen and elastin fibers. Hyaluronic acid is the most abundant glycosaminoglycan in the skin. It is the main component of the dermis and is also present around the keratinocytes in the epidermis. GAGs are incredibly hygroscopic molecules which are able to retain up to one thousand times their weight in water (J E. Silbert, Proteoglycans and glycosaminoglycans. In: Goldsmith L A, ed. Biochemistry and Physiology of the Skin. New York, N.Y.: Oxford University; 1983: 448-461). Due to these exceptional properties, glycosaminoglycan and collagen complexes are the main agents for storing water in the extracellular matrices.
Cutaneous water loss can have several origins: hereditary, acquired or environmental. In a very dry environment, water loss by evaporation from the stratum corneum is significant and can exceed the rate of replacement by transcellular diffusion.
During cutaneous ageing, the skin becomes dry. Thus, it is very often observed among older subjects, in particular those over the age of 50, that xerosis or the drying up of mucus membranes linked to a lower level of sebum secretion, to changes in hormone levels or to a slowing down in water flow across the epidermis, manifests. The skin is therefore the main location for itching and tautness, two symptoms which are characteristic of dry skin. Xerosis induced by photochemotherapy and eczema are examples of acquired conditions manifesting in dryness of skin. Sjögren's Syndrome or neck radiotherapy can be cited as examples of acquired conditions which result in dryness of the mouth, or xerostomia. Finally ocular or vaginal dryness are examples of conditions involving a drying of mucus membranes.
A first alternative for treating dry skin consists of topically administering products designed for restoring the cutaneous barrier, or film-forming agents designed to retain water. However, these products act superficially and do not correct the biological defects of skin suffering from chronic dehydration. FR 2 801 504 and FR 2 874 502 can also be cited, which describe the use of plant extracts to stimulate aquaporin activity and to improve skin moisturization. Despite everything, these active ingredients do not allow an improvement in the constituent moisturization of all the parts of the skin. Peptide extracts of pea have been described for their pigmenting effect (FR 2 904 556) or their desquamation effect (JP 09025225), but have never described the beneficial effect on skin moisturization.
The inventors have now shown that the use of a peptide hydrolysate of pea (Pisum sativum L.) as an active agent capable of activating the expression of aquaporins, glycosaminoglycans and filaggrin, produces an overall improvement in the constituent moisturization of skin.